Microscopic mechanical systems have been evolving for use in devices for sensing acceleration, pressure, and chemical composition, and have also been used as actuators, such as moving mirrors, shutters, and aerodynamic control surfaces. More particularly, micromechanical systems have been proposed for use in fluid control, such as in medical pharmaceuticals, bearing lubricators and miniature space systems. Many types of fluid flow control systems require the use of pumps and valves. Developments in miniaturization and large-scale integration in fluidics have led to the concept of creating microfluidic devices on a microscopic scale.
One category of functions essential to many microfluidic analysis processes involves separations, and includes such functions as concentration, separation, and purification. These functions are based on the need to increase or decrease the concentration of a solute relative to a solvent, or suspended particulates relative to a carrier. In macroscopic systems, methods employed for this function include filtration, evaporation, and chromatography, none of which, for various reasons, are easily implemented in microfluidic systems. Thus far, researchers experimenting with freezing as a method of separation on the macroscopic scale have met with limited success.
Freeze concentration is based on the phenomenon of exclusion of solute molecules or particulates during crystallization of a solvent. For example, freezing a sample of salt water will produce a number of crystals of relatively pure water separated by regions of brine (either solid or liquid, depending of the final temperature of the sample). There are a number of difficulties associated with actually implementing freeze concentration techniques. Once the sample is frozen, it is not possible to separate the regions of relatively high and low concentrations of the solute because they are thoroughly interlocked, where this results from the difficulty in providing precise control of the freezing process.
A key problem is that an advancing ice front will push any solute ahead of it, causing a local buildup of solute concentration immediately adjacent to the ice front that will normally dissipate only through diffusion, which is an inherently slow process. As the solute concentration gets higher, the freezing point of the liquid is decreased. The temperature of the ice thus has to get well below the normal freezing point of the liquid in order to induce further growth of the ice. The proximity of the sub-cooled ice and the relatively warmer liquid beyond the region of elevated solute concentration sets up a thermal gradient in the liquid, where the temperature of the liquid immediately adjacent to the ice is below the normal freezing point of water. If the solute concentration gradient is sufficiently steep compared to the thermal gradient, then the gradient in the local freezing point of the fluid will be steeper than the thermal gradient in the fluid. Under these conditions, the planar ice front becomes unstable, leading to a dendritic growth process in which tree-like solid structures form. The dendrites trap regions of high solute concentration. If the temperature gradient is steep enough relative to the concentration gradient, it may also be possible for freezing to nucleate in the fluid at a point some distance away from the ice front and beyond the region of high solute concentration, again trapping solute between layers of ice. In either case, the end result is a random collection of ice crystals trapping bands of high solute concentration between adjacent ice layers. Because the freezing occurs irregularly, the bands of high solute concentration are irregular in shape, and cannot be easily separated from the relatively pure ice crystals.
Due to these difficulties associated with freeze separation on the macroscopic scale and to the lack of experience in providing proper temperature controls on the microscopic scale, freeze separation has not previously been considered possible for microfluidic devices. There is a need for improved methods for achieving separations in microfluidic devices.